1. Noncardiac Indications: Aetna considers single photon emission computed tomography (SPECT) medically necessary for any of the following indications:
   
   
   1. Diagnosing and assessing hemangiomas of the liver; or
   2. Presurgical ictal detection of seizure focus in members with epilepsy (in place of positron emission tomography (PET)); or
   3. Assessment of osteomyelitis, to distinguish bone from soft tissue infection; or
   4. Localization of abscess, for suspected or known localized infection or inflammatory process; or
   5. Differentiation of necrotic tissue from tumor of the brain; or
   6. Lymphoma, to distinguish tumor from necrosis; or
   7. Neuroendocrine tumors, diagnosis and staging; or
   8. Detection of spondylolysis and stress fractures; or
   9. Imaging of parathyroids in parathyroid disease.
      
      
2. Aetna considers SPECT experimental and investigational for all other noncardiac indications, including any of the following, because its diagnostic value has not been established in the peer reviewed medical literature in these situations:
   
   
   1. Initial or differential diagnosis of members with suspected dementia (e.g., Alzheimer's disease, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia); or
   2. Diagnosis or assessment of stroke members; or
   3. Scanning of internal carotid artery during temporary balloon occlusion; or
   4. Diagnosis or assessment of members with attention deficit/hyperactivity disorder (CPB 426 - Attention Deficit/Hyperactivity Disorder); or
   5. Diagnosis or assessment of members with autism (CPB 648 - Pervasive Developmental Disorders); or
   6. Diagnosis or assessment of members with personality disorders (e.g., borderline personality disorder, anti-social personality disorder including psychopathy, schizotypal personality disorder, as well as aggressive and violent behaviors); or
   7. Diagnosis or assessment of members with schizophrenia; or
   8. Differential diagnosis of Parkinson's disease from other Parkinsonian syndromes; or
   9. Prosthetic graft infection; or
   10. Vasculitis.
       
       
3. Cardiac Indications: Aetna considers SPECT medically necessary for the following indications for members who do not meet any of the exclusion criteria below:
   
   
   1. Diagnosis of coronary artery disease (CAD) in members with an uninterpretable resting electrocardiogram (ECG) and restricted exercise tolerance; or
   2. Assessing myocardial viability before referral for myocardial revascularization procedures.
      
      
4. Aetna considers SPECT experimental and investigational for all other cardiac indications.
   
   Exclusion criteria: Aetna considers SPECT myocardial perfusion imaging experimental and investigational for the following indications for which the study is considered “inappropriate” according to appropriateness criteria from the American College of Cardiology (Brindis, et al., 2005):
   
   
   1. Screening of members without chest pain or equivalent symptoms when there is a low probability of coronary disease (Framingham score less than 10)* and no history of diabetes; or
   2. Screening of members with chest pain or chest pain equivalent symptoms when there is a low probability of coronary disease (Framingham score less than 10)*, no history of diabetes, and there are no impediments or contraindications to non-nuclear stress testing**; or
   3. Prior to low risk† non-cardiac surgery for risk assessment; or
   4. Prior to intermediate risk† non cardiac surgery if the member is capable of, and has no contraindication to standard stress testing**; or
   5. Prior to high risk† surgery when the member is asymptomatic and there was a normal cardiac catheterization, coronary intervention (percutaneous transluminal coronary angioplasty (PTCA), stenting, coronary artery bypass grafting (CABG)), or normal nuclear stress test less than one year before the surgical date; or
   6. As a routine screening evaluation after a PTCA with or without stenting or CABG prior to discharge from the acute care setting; or
   7. In the setting of acute chest pain or equivalent symptoms with a high likelihood of being acute coronary syndrome, when there has been a diagnosis of acute myocardial infarction, in the immediate post thombolytic period, or when there is a high pretest likelihood of significant coronary disease as demonstrated by marked ST segment elevation on the ECG; or
   8. Evaluation of a member with an acute coronary event and hemodynamic instability, shock, or mechanical complications of the event; or
   9. Reevaluation of members without chest pain or equivalent symptoms, without known coronary disease, at high risk for coronary disease (based upon the Framingham score greater than 10)*, who have an initial negative radionuclear imaging study, when it has been less than two years since the last radionuclear study; or
   10. Reevaluation of members without chest pain or equivalent symptoms or with stable symptoms, with known coronary disease as determined by prior abnormal catheterization or SPECT cardiac study (but without prior infarction), when it has been less than one year since the last radionuclear study. Note: if the member has worsening symptoms or if the member had silent ischemia, more frequent imaging or other diagnostic testing or interventions may be medically necessary; or
   11. As a routine screening evaluation after a revascularization procedure (PTCA with stenting or coronary artery bypass surgery (CABG)) at an interval of less than two years from the procedure if there is no worsening in the members symptomatology and if the member had symptoms prior to the intervention, and there is no history of congestive heart failure. Note: If there is a history of congestive heart failure and the member is status post revascularization, repeat nuclear imaging as frequently as annually may be medically necessary; or
   12. Assessment of vulnerable plaque.

* A tool for calculating Framingham score is available from the National Heart Lung and Blood Institute at the following website: http://hp2010.nhlbihin.net/atpIII/calculator.asp?usertype=prof

** According to ACC guidelines, the following are impediments or contraindications to nonnuclear stress testing:

1. a history of prior proven ischemic cardiac events; or
2. proven coronary artery disease by past SPECT or coronary catheterization; or
3. a history of physical impairments that would preclude physically performing the exercise portion of a stress test; or
4. the members ECG would prevent interpretation of a standard stress testing by being “uninterpretable” during the test, i.e., left bundle branch block (LBBB), paced rhythm, Wolf Parkinson White syndrome, left ventricular hypertrophy (LVH) with ST segment depression, or digoxin use.

† Surgical risk categories.

• High-risk surgery (risk of cardiac death or myocardial infarction (MI) greater than 5%): emergent major operations (particularly in the elderly), aortic and peripheral vascular surgery, prolonged surgical procedures associated with large fluid shifts and/or blood loss.
• Intermediate-risk surgery (risk of cardiac death or MI 1% to 5%): carotid endarterectomy, head and neck surgery, surgery of the chest or abdomen, orthopedic surgery, prostate surgery.
• Low-risk surgery (cardiac death or MI less than 1%): endoscopic procedures, superficial procedures, cataract surgery, breast surgery.

Source: ACC (2005).

Single photon emission computed tomography (SPECT) is a nuclear medicine technique that uses radiopharmaceuticals, a rotating camera (single or multiple-head), and a computer to produce images representing slices through the body in different planes. SPECT images are functional in nature rather than being purely anatomical such as ultrasound, CT, and MRI.

SPECT for Myocardial Perfusion Imaging

SPECT has been applied to the heart for myocardial perfusion imaging. SPECT is an effective noninvasive diagnostic technology when evaluating patients for clinically significant coronary artery disease (CAD) in the following circumstances: for diagnosing CAD in patients with an abnormal resting electrocardiogram (ECG) and restricted exercise tolerance; or assessing myocardial viability before referral for myocardial revascularization.

SPECT has a far greater sensitivity for detecting silent ischemia than stress ECG. Pooled data of exercise SPECT studies in over 1000 patients revealed a 90 percent overall sensitivity for detecting CAD. In assessing myocardial viability, studies indicate that, even in patients with severe irreversible thallium defects on standard exercise-redistribution imaging, thallium re-injection provides information regarding myocardial viability that is comparable to that provided by PET.

SPECT for Detection of Neurological Diseases

SPECT examines cerebral function by documenting regional blood flow and metabolism. SPECT of the brain is a useful alternative to PET for the presurgical ictal detection of seizure focus Effective surgical treatment of patients with intractable epilepsy is dependent on accurate localization of the epileptic focus and precise delineation of the epileptogenic region. It is generally agreed that this requires EEG recording with electrocorticography. This testing is designed to identify the source or sources of the seizures, as well as an assessment of brain function. The search for non-invasive and cost-effective means of seizure localization has been an important area of research.

Seizures are associated with dramatic increases in blood flow, localized in partial seizures and global during generalized seizures. Ictal SPECT uses the physiologic increase in regional cerebral blood blow during seizures to potentially localize the epileptogenic region. Ictal studies, although more difficult logistically, are reported to have a sensitivity of 81 to 93 percent. (Interictal SPECT demonstrates hypoperfusion and is reported to have a sensitivity ranging from 40 to 75 percent.)

Other imaging modalities help in localizing abnormal epileptogenic tissue. Quantitative MRI has a sensitivity of 80 to 90 percent for the lateralization of temporal lobe epilepsy. However, there are instances where ictal SPECT has identified lesions not detected by MRI. Depth electrocorticography and intraoperative electrocorticography, though accurate in many forms of epilepsy, are both highly invasive. In cortical developmental disorders, these EEG techniques often fail to localize the epileptogenic area. SPECT imaging may offer a safe and accurate alternative.

Ictal SPECT testing requires that seizure activity be provoked through reduction of antiepileptic medications. Video EEG monitoring may also be performed. Due to the nature of ictal SPECT, it should be performed in a hospital setting.

Studies of SPECT in the interictal or postictal detection of seizure focus, determination of seizure subtypes and monitoring of drug therapy for epilepsy have not established its efficacy for these indications.

Clinical studies indicate that SPECT is more accurate at detecting acute ischemia than CT scan. By eight hours after infarction, about 20 percent of CT scans will be positive but nearly 90 percent of SPECT scans will be. Beyond 72 hours, the sensitivities of CT and SPECT are nearly identical. In addition, the defects noted on SPECT are frequently larger than those noted on CT studies.

Among the treatments of acute ischemic stroke, the use of t-PA has been shown to reduce neurologic impairment if administered within three hours of onset. This is administered when CT is negative for hemorrhage. SPECT cannot detect hemorrhage in order to rule out use of thrombolysis. Therefore, while SPECT is more sensitive than CT in detecting ischemia, it has not been shown to be useful in detecting ischemia early enough to play a role in the use of thrombolysis. Studies using SPECT in the presence of CVA have timed its performance at less than 6 hours to less than 14 days from the time of onset.

Studies have also reported on SPECT's value with regard to the assessment of prognosis after stroke, determination of stroke type, monitoring therapies used post-stroke, diagnosis of vasospasm following subarachnoid hemorrhage and in the diagnosis/prognosis regarding transient ischemic attacks (TIAs). SPECT may prove to be helpful in these applications in the future.

SPECT has proven useful in distinguishing recurrent brain tumor from radiation necrosis. Radiation necrosis needs to be distinguished from recurrent brain tumor to determine whether chemotherapy is necessary. Radiation necrosis is more common in brain tumor patients receiving local boost irradiation. Radiation necrosis and brain tumor may have similar clinical signs and symptoms, and are not reliably distinguished clinically.

SPECT has been studied in the diagnosis of patients with Alzheimer's disease.  At present, the definitive diagnosis of Alzheimer's disease can only be made on pathologic examination of brain tissue.  Alzheimer's disease is largely a diagnosis of exclusion.  The diagnostic evaluation of the demented patient is therefore aimed largely at identifying other potentially treatable causes of cognitive impairment. A technology assessment of SPECT for dementia and Alzheimer's disease prepared by the Institute for Clinical Effectiveness and Health Policy (Ferrante, 2004) concluded: "SPECT has not clearly demonstrated its usefulness in assessing patients with dementia, and it has no precise indications for diagnosis, evaluation of prognosis or monitoring response to treatment."

In Alzheimer's disease, SPECT shows decreased perfusion in the association cortex of the parietal lobe and the posterior temporal regions. Frontal association cortex is predominantly affected in some cases, but usually is not involved until late in the course of the disease. The occipital lobes are less involved and the paracentral cortex is spared. Although SPECT studies have been reported in over 500 patients with Alzheimer's disease, in most cases the diagnosis was made clinically and only in 53 patients it was confirmed by autopsy. Controlled studies of SPECT in Alzheimer's disease have shown a sensitivity of this procedure to vary from 50 to 95 percent. The best results have been reported in the more recent studies, using higher resolution equipment. In the 2001 practice parameter on the diagnosis of dementia, the American Academy of Neurology does not recommend SPECT for routine use in either initial or differential diagnosis of dementia (Knopman et al, 2001).

Neuroimaging markers are increasingly important in the early diagnosis of the dementias, not only to detect the rare tumor, but also to differentiate the various types of neurodegenerative dementias. The potential of MRI and PET as surrogates for disease progression for therapeutic trials is being examined in a large multi-center trial. However, SPECT has been reported to show specific findings in both frontotemporal dementia (FTD) and Alzheimer disease (AD) and is much more available and less expensive than PET. McNeil et al (2007) evaluated the diagnostic accuracy of technetium-99–labeled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD and 31 pathologically confirmed cases of AD. A nuclear medicine physician, blinded to the clinical findings, rated the images. Except in the case of 1 FTD patient, for whom neuropsychological data were unavailable, the clinical and neuropsychological evaluation was more accurate than SPECT alone in predicting the histological diagnosis.

SPECT has also been reported to be used in neoplasms (grading of gliomas), HIV encephalopathy, head trauma, Huntington's chorea, persistent vegetative states and in diagnosing brain death. Based upon the current evidence, SPECT has not proven to be established in any of these clinical situations. More study is needed in these areas.

The FDA has approved four radiopharmaceuticals for imaging of the brain: I-123 isopropyliodoamphetamine (IMP, Spectamine); Tc-99m HMPAO (hexamethyl propylamine oxime, Ceretec); Tc-99m ECD (ethyl cysteinate dimer, Neurolite), and thallium 201 diethyldithiocarbamate (T1-DDC).

SPECT for the Liver

Hemangiomas are the most common benign lesion of the liver. It is important to differentiate these lesions from others that may be malignant. Because of the risk of hemorrhage inherent in a percutaneous biopsy of liver hemangiomas, noninvasive modalities have been used for differentiation. Hepatic hemangiomas are so vascular that their blood pool is easily differentiated from other solid hepatic masses by nuclear scanning with labeled red blood cells (RBCs). The labeled RBCs are injected intravenously and resolution is markedly improved with SPECT. Review articles and published studies support SPECT as an appropriate diagnostic modality to differentiate hepatic lesions as hemangiomas.

SPECT for Neuroendocrine Tumors

Carcinoids and other neuroendocrine tumors have somatostatin receptors; therefore, they can be imaged with somatostatin analogues (octreotide, pentetreotide) tagged with an appropriate radioisotope (Khan & Jones, 2005). Single photon emission CT (SPECT) and subtraction techniques improve detection. An assessment from the Australian Medical Services Advisory Committee stated that SPECT is often performed in conjunction with antibody imaging (Octreoscan) of neuroendocrine tumors, usually at 24 and occasionally at 48 hours after the injection. The assessment explained that SPECT is able to differentiate more easily between areas of pathological uptake and physiological uptake in the abdomen. The assessment explained that SPECT can also help to discriminate between mesenteric and bone lesions. The assessment noted that extra-planar images may be obtained from areas of specific interest, using longer exposure time for more easily interpreted imaging.

SPECT for Spondylolysis and Stress Fractures

The role of SPECT of the spine has changed in recent years with the wide availability of MRI and especially contrast-enhanced MRI. Bone scanning with SPECT of the spine may allow for visualization of lesions related to stress fractures or stress reactions in the spine such as spondylolysis.  SPECT has been accepted as extremely sensitive in detecting incipient spondylolysis and stress/insufficiency fractures  (Manaster, et al., 2005). SPECT shows stress fractures days to weeks earlier than radiographs in many instances, and differentiate between osseous and soft tissue injury as well. However, in most cases bone scans lack specificity and supplemental imaging may be necessary for conclusive diagnosis or to avoid false positives. SPECT continues to be used in back pain, especially in children and adolescents, to detect incipient spondylolysis that may not be detected by conventional imaging. Because of the sensitivity of SPECT scans, 80% of all fractures show an abnormality 24 hours post injury and 95% at 72 hours. A normal scan generally excludes the diagnosis of stress/insufficiency fracture, and the patient may return to normal activity.

SPECT for the Internal Carotid Artery

Internal carotid artery temporary balloon occlusion (TBO) test is a well-established part of the preoperative evaluation of patients with aneurysm or tumor involving the neck or skull base in whom arterial sacrifice or prolonged temporary occlusion is considered a possible part of the surgical or endovascular therapy. TBO is performed in conjunction with cerebral blood flow analysis to identify those patients who will not tolerate permanent carotid occlusion. Traditionally, xenon-enhanced CT has been used during TBO to detect signs of ischemia; however, SPECT has recently been reported as a method to detect focal hypoperfusion during test occlusion. Several small studies in the published literature report preliminary results that SPECT scanning during TBO is a safe and effective method to assess cerebral blood flow. However, it is premature to recommend SPECT over the conventional xenon-enhanced CT.

SPECT for the Diagnosis/Assessment of Attention Deficit/Hyperactivity Disorder

Functional neuroimaging such as PET and SPECT has been used to study patients with attention deficit/hyperactivity disorder (ADHD). Although some studies have shown differences in brain structure or function comparing children with and without ADHD, these findings do not differentiate reliably between children with and without this disorder (i.e., although group means may differ significantly, the overlap in findings among children with and without ADHD results in high rates of false-positives and false-negatives). As a result, SPECT should not be used as a screening or diagnostic tool for children with ADHD. The American Academy of Pediatrics' Practice Guideline on “Diagnosis and Evaluation of the Child with Attention-Deficit/Hyperactivity Disorder” does not recommend neuroimaging studies in the diagnosis of ADHD. An evidence review by McGough and Barkley (2004) stated that there are insufficient scientific data to justify use of laboratory assessment measures, including neuropsychological tests and brain imaging, in diagnosing adult ADHD.

SPECT for the Diagnosis/Assessment of Autism

The American Academy of Neurology (2000) stated that there is no evidence to support a role of neuroimaging modalities such as SPECT in the clinical diagnosis of autism.

Other Indications

SPECT has proven useful in distinguishing lymphoma from necrosis in the chest and abdomen. It is also useful in localizing abscesses, and distinguishing abscess from other infectious or inflammatory processes. SPECT is also useful in osteomyelitis in distinguishing inflammation of soft tissue from bone.

Guidelines on parathyroid scintigraphy from the Society of Nuclear Medicine (Greenspan, et al., 2004) state that there is a developing consensus that SPECT imaging is useful, because, when used in conjunction with planar imaging, SPECT provides increased sensitivity and more precise anatomic localization. They note that this is particularly true in detecting both primary and recurrent hyperparathyroidism resulting from ectopic adenomas. In the mediastinum, accurate localization may assist in directing the surgical approach, such as median sternotomy versus left or right thoracotomy.

In a review on neuroimaging in psychopathy (including anti-social personality disorder and violent behavior), Pridmore, et al. (2005) noted that functional neuroimaging strongly suggests dysfunction of particular frontal and temporal lobe structures in subjects with psychopathy. However, there are difficulties in selecting homogeneous index cases and appropriate control groups. These investigators stated that further studies are needed.

An assessment of SPECT for schizophrenia by the Institute for Clinical Effectiveness and Health Policy (Pichon Riviere, et al., 2004) found that SPECT has identified increases in dopaminergic activity in the striated body and other areas of the brain during the episodes of schizophrenia exacerbation. SPECT has also been able to identify decreases in frontal cortex uptake that are associated with negative symptoms of schizophrenia. The investigators, however, were unable to find substantial evidence for the role of SPECT scans in therapeutic decision-making in schizophrenia. They concluded that the use of SPECT scan in schizophrenia remains investigational.

In the recent practice parameter on the diagnosis and prognosis of new onset PD (an evidence-based review) by the American Academy of Neurology (AAN), Suchowersky, et al. (2006) stated that SPECT scanning may not be useful in differentiating Parkinson's disease from other parkinsonian syndromes.

In a meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes, Vlaar and colleagues (2007) concluded that SPECT with pre-synaptic radiotracers is relatively accurate to differentiate patients with PD in an early phase from normalcy, patients with PD from those with essential tremor, and PD from vascular parkinsonism. The accuracy of SPECT with both pre-synaptic and post-synaptic tracers to differentiate between PD and atypical parkinsonian syndrome is relatively low.

van der Vaart et al (2008) described the current applications of PET and SPECT as a diagnostic tool for vascular disease as relevant to vascular surgeons. These researchers noted that PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. Moreover, the authors stated that considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of interdisciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.